Exploring the genetic interaction between ERAP1/ERAP2 and HLA-B*52:01 in Takayasu arteritis

Takayasu arteritis is a rare vasculitis characterized by inflammation of large arteries. Given the robust genetic association with HLA-B*52:01, it was recently proposed to classify Takayasu arteritis within the spectrum of MHC-I-opathies. Although genetic associations in ERAP1 and ERAP2 have been described in several MHC-I-opathies, their role in Takayasu arteritis remains unclear. This study investigated the genetic interaction between ERAP1/ERAP2 and HLA-B*52:01 in Takayasu arteritis.

Using data from a large multi-ancestral GWAS, we examined the genetic association between ERAP1 and ERAP2 polymorphisms with Takayasu arteritis. Next, we conducted genetic interaction analyses between ERAP1/ERAP2 polymorphisms and HLA-B*52:01, followed by a meta-analysis across populations. In addition, we conducted a genetic association test for ERAP1/ERAP2 polymorphisms restricted to HLA-B*52:01-positive individuals.

Our analyses suggested no significant genetic interactions between ERAP1 or ERAP2 and HLA-B*52:01 in Takayasu arteritis, which contrasts with the findings observed in other MHC-I-opathies. In addition, no significant associations between ERAP1/ERAP2 and Takayasu arteritis were detected, including analyses under dominant or recessive models, or after stratifying by HLA-B*52:01 status.

These results suggest that the genetic profile of Takayasu arteritis differs from other MHC-I-opathies, supporting its classification as a distinct subtype within this group of immune-mediated diseases. These finding are hypothesis-generating, and validation in larger cohorts is warranted.